Generation of Protective T Cell-Independent Antiviral Antibody Responses in SCID Mice Reconstituted with Follicular or Marginal Zone B Cells

Generation of Protective T Cell-Independent Antiviral Antibody Responses in SCID Mice Reconstituted with Follicular or Marginal Zone B Cells
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DOI:
10.4049/jimmunol.0900068
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发表时间:
2009-07-01
影响因子:
4.4
通讯作者:
Szomolanyi-Tsuda, Eva
Szomolanyi-Tsuda, Eva
中科院分区:
医学2区
文献类型:
--
作者:
Guay, Heath M.;Mishra, Rabinarayan;Szomolanyi-Tsuda, Eva

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成年小鼠骨髓中产生的B细胞作为过渡性B细胞进入外周,随后分化成两种表型和功能不同的亚群之一,边缘区(MZ)或滤泡(Fo)B细胞。然而,最近的报道表明,响应于环境因素,如淋巴细胞减少,成熟的Fo B细胞可以改变以显示MZ B细胞的表型标志物特征。以前,我们发现转移到SCID小鼠的脾B细胞对多瘤病毒(PyV)感染有反应,具有T细胞依赖性(TI)IgM和IgG分泌,减少病毒载量并保护小鼠免受感染的致死作用。然而,MZ和Fo B细胞亚群对这种抗病毒TI-2应答的贡献尚未得到解决。在这项研究中,我们表明,分选纯化的MZ和Fo B细胞转移到SCID小鼠时,对PyV感染产生保护性TI Ab反应。此外,在PyV感染的SCID小鼠的脾脏中转移的Fo B细胞改变表型,其中许多显示MZ B细胞特征。这些发现证明了病毒感染宿主中B细胞亚群的可塑性,并首次表明完全来源于Fo B细胞的B细胞可有效地在抗病毒TI-2应答中发挥作用。免疫学杂志,2009,183:518-523.
B cells generated in the bone marrow of adult mice enter the periphery as transitional B cells and subsequently differentiate into one of two phenotypically and functionally distinct subsets, marginal zone (MZ) or follicular (Fo) B cells. Recent reports indicate, however, that in response to environmental cues, such as lymphopenia, mature Fo B cells can change to display phenotypic markers characteristic of MZ B cells. Previously, we found that splenic B cells transferred to SCID mice responded to polyoma virus (PyV) infection with T cell-in dependent (TI) IgM and IgG secretion, reducing the viral load and protecting mice from the lethal effect of the infection. The contribution of MZ and Fo B cell subsets to this antiviral TI-2 response, however, has not been addressed. In this study, we show that both sort-purified MZ and Fo B cells generate protective TI Ab responses to PyV infection when transferred into SCID mice. Moreover, the transferred Fo B cells in the spleens of the PyV-infected SCID mice change phenotype, with many of them displaying MZ B cell characteristics. These findings demonstrate the plasticity of the B cell subsets in virus-infected hosts and show for the first time that B cells derived exclusively from Fo B cells can effectively function in antiviral TI-2 responses. The Journal of Immunology, 2009, 183: 518-523.